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Objectives: Differentiating true progression or recurrence (TP/TR) from therapy-related changes (TRC) is complex in brain tumours. Amide proton transfer-weighted (APT) imaging is a chemical exchange saturation transfer (CEST) MRI technique that may improve diagnostic accuracy during radiological follow-up. This systematic review and meta-analysis elucidated the level of evidence and details of state-of-the-art imaging for APT-CEST in glioma and brain metastasis surveillance., Methods: PubMed, EMBASE, Web of Science, and Cochrane Library were systematically searched for original articles about glioma and metastasis patients who received APT-CEST imaging for suspected TP/TR within 2 years after (chemo)radiotherapy completion. Modified Quality Assessment of Diagnostic Accuracy Studies-2 criteria were applied. A meta-analysis was performed to pool results and to compare subgroups., Results: Fifteen studies were included for a narrative synthesis, twelve of which (500 patients) were deemed sufficiently homogeneous for a meta-analysis. Magnetisation transfer ratio asymmetry performed well in gliomas (sensitivity 0.88 [0.82-0.92], specificity 0.84 [0.72-0.91]) but not in metastases (sensitivity 0.64 [0.38-0.84], specificity 0.56 [0.33-0.77]). APT-CEST combined with conventional/advanced MRI rendered 0.92 [0.86-0.96] and 0.88 [0.72-0.95] in gliomas. Tumour type, TR prevalence, sex, and acquisition protocol were sources of significant inter-study heterogeneity in sensitivity (I 2  = 62.25%; p < 0.01) and specificity (I 2  = 66.31%; p < 0.001)., Conclusion: A growing body of literature suggests that APT-CEST is a promising technique for improving the discrimination of TP/TR from TRC in gliomas, with limited data on metastases., Clinical Relevance Statement: This meta-analysis identified a utility for APT-CEST imaging regarding the non-invasive discrimination of brain tumour progression from therapy-related changes, providing a critical evaluation of sequence parameters and cut-off values, which can be used to improve response assessment and patient outcome., Key Points: Therapy-related changes mimicking progression complicate brain tumour treatment. Amide proton imaging improves the non-invasive discrimination of glioma progression from therapy-related changes. Magnetisation transfer ratio asymmetry measurement seems not to have added value in brain metastases., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is V.C.K. Conflict of interest: V.C.K. is a Junior Deputy Editor for European Radiology. They have not participated in the selection or review processes. The remaining authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: One of the authors has significant statistical expertise. Informed consent: Written informed consent was not required for this study because of the study type. Ethical approval: Institutional Review Board approval was not required because it is not necessary for a review. Study subjects or cohorts overlap: Some study subjects or cohorts have been previously reported in the cited source articles (as is normal for a systematic review). Methodology: Retrospective Multicenter study, (© 2024. The Author(s).)

Purpose: This guideline will discuss radiotherapeutic management of IDH-mutant grade 2 and grade 3 diffuse glioma, using the latest 2021 WHO (5th) classification of brain tumours focusing on: imaging modalities, tumour volume delineation, irradiation dose and fractionation., Methods: The ESTRO Guidelines Committee, CNS subgroup, nominated 15 European experts who identified questions for this guideline. Four working groups were established addressing specific questions concerning imaging, target volume delineation, radiation techniques and fractionation. A literature search was performed, and available literature was discussed. A modified two-step Delphi process was used with majority voting resulted in a decision or highlighting areas of uncertainty., Results: Key issues identified and discussed included imaging needed to define target definition, target delineation and the size of margins, and technical aspects of treatment including different planning techniques such as proton therapy., Conclusions: The GTV should include any residual tumour volume after surgery, as well as the resection cavity. Enhancing lesions on T1 imaging should be included if they are indicative of residual tumour. In grade 2 tumours, T2/FLAIR abnormalities should be included in the GTV. In grade 3 tumours, T2/FLAIR abnormalities should also be included, except areas that are considered to be oedema which should be omitted from the GTV. A GTV to CTV expansion of 10 mm is recommended in grade 2 tumours and 15 mm in grade 3 tumours. A treatment dose of 50.4 Gy in 28 fractions is recommended in grade 2 tumours and 59.4 Gy in 33 fractions in grade 3 tumours. Radiation techniques with IMRT are the preferred approach., Competing Interests: Declaration of competing interest MvdB: Receipt of grant/research support from Boehringer-Ingelheim, and receipt of honoraria or consultation fees from Boehringer-Ingelheim, Servier, Genenta, Nerviano, Incyte, Chimerix, Fore Biotherapeutics. Participated in a company sponsored speaker’s bureau for Servier; NG: Receipt of grant/research support from German Research Council (project number 428090865/SPP 2177), and receipt of honoraria or consultation fees from Blue Earth Diagnostics, Telix Pharmaceuticals; GM: Receipt of grant/research support from Horizon EU-funded LEGATO-Trial, and receipt of honoraria or consultation fees from Servier, AstraZeneca, Novocure; VK: Receipt of grant/research support from Hanarth Stichting, and receipt of honoraria or consultation fees from Eli Lilly (Consultation fees). Bayer stock shareholder; MN: Receipt of grant/research support from Deutsche Krebshilfe (DKH), Brainlab AG, Elekta AB, and participated in a company sponsored speaker’s bureau for AstraZeneca, Brainlab AG; SE: Receipt of honoraria or consultation fees from Servier; UR: Receipt of grant/research support from Institutional research grants from Brainlab, and receipt of honoraria or consultation fees from AstraZeneca, Accuray; RR: Receipt of grant/research support from Institutional research grants from Bayer, and receipt of honoraria or consultation fees from Novocure, Servier, Genenta, CureVac., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background and Purpose: To develop and test a decision tree for predicting contrast enhancement quality and shape using precontrast magnetic resonance imaging (MRI) sequences in a large adult-type diffuse glioma cohort., Methods: Preoperative MRI scans (development/optimization/test sets: n = 31/38/303, male = 17/22/189, mean age = 52/59/56.7 years, high-grade glioma = 22/33/249) were retrospectively evaluated, including pre- and postcontrast T1-weighted, T2-weighted, fluid-attenuated inversion recovery, and diffusion-weighted imaging sequences. Enhancement prediction decision tree (EPDT) was developed using development and optimization sets, incorporating four imaging features: necrosis, diffusion restriction, T2 inhomogeneity, and nonenhancing tumor margins. EPDT accuracy was assessed on a test set by three raters of variable experience. True enhancement features (gold standard) were evaluated using pre- and postcontrast T1-weighted images. Statistical analysis used confusion matrices, Cohen's/Fleiss' kappa, and Kendall's W. Significance threshold was p < .05., Results: Raters 1, 2, and 3 achieved overall accuracies of .86 (95% confidence interval [CI]: .81-.90), .89 (95% CI: .85-.92), and .92 (95% CI: .89-.95), respectively, in predicting enhancement quality (marked, mild, or no enhancement). Regarding shape, defined as the thickness of enhancing margin (solid, rim, or no enhancement), accuracies were .84 (95% CI: .79-.88), .88 (95% CI: .84-.92), and .89 (95% CI: .85-.92). Intrarater intergroup agreement comparing predicted and true enhancement features consistently reached substantial levels (≥.68 [95% CI: .61-.75]). Interrater comparison showed at least moderate agreement (group: ≥.42 [95% CI: .36-.48], pairwise: ≥.61 [95% CI: .50-.72]). Among the imaging features in the EPDT, necrosis assessment displayed the highest intra- and interrater consistency (≥.80 [95% CI: .73-.88])., Conclusion: The proposed EPDT has high accuracy in predicting enhancement patterns of gliomas irrespective of rater experience., (© 2024 The Author(s). Journal of Neuroimaging published by Wiley Periodicals LLC on behalf of American Society of Neuroimaging.)

Objectives: To develop a gadolinium-free MRI-based diagnosis prediction decision tree (DPDT) for adult-type diffuse gliomas and to assess the added value of gadolinium-based contrast agent (GBCA) enhanced images., Materials and Methods: This study included preoperative grade 2-4 adult-type diffuse gliomas (World Health Organization 2021) scanned between 2010 and 2021. The DPDT, incorporating eleven GBCA-free MRI features, was developed using 18% of the dataset based on consensus readings. Diagnosis predictions involved grade (grade 2 vs. grade 3/4) and molecular status (isocitrate dehydrogenase (IDH) and 1p/19q). GBCA-free diagnosis was predicted using DPDT, while GBCA-enhanced diagnosis included post-contrast images. The accuracy of these predictions was assessed by three raters with varying experience levels in neuroradiology using the test dataset. Agreement analyses were applied to evaluate the prediction performance/reproducibility., Results: The test dataset included 303 patients (age (SD): 56.7 (14.2) years, female/male: 114/189, low-grade/high-grade: 54/249, IDH-mutant/wildtype: 82/221, 1p/19q-codeleted/intact: 34/269). Per-rater GBCA-free predictions achieved ≥ 0.85 (95%-CI: 0.80-0.88) accuracy for grade and ≥ 0.75 (95%-CI: 0.70-0.80) for molecular status, while GBCA-enhanced predictions reached ≥ 0.87 (95%-CI: 0.82-0.90) and ≥ 0.77 (95%-CI: 0.71-0.81), respectively. No accuracy difference was observed between GBCA-free and GBCA-enhanced predictions. Group inter-rater agreement was moderate for GBCA-free (0.56 (95%-CI: 0.46-0.66)) and substantial for GBCA-enhanced grade prediction (0.68 (95%-CI: 0.58-0.78), p = 0.008), while substantial for both GBCA-free (0.75 (95%-CI: 0.69-0.80) and GBCA-enhanced (0.77 (95%-CI: 0.71-0.82), p = 0.51) molecular status predictions., Conclusion: The proposed GBCA-free diagnosis prediction decision tree performed well, with GBCA-enhanced images adding little to the preoperative diagnostic accuracy of adult-type diffuse gliomas., Key Points: Question Given health and environmental concerns, is there a gadolinium-free imaging protocol to preoperatively evaluate gliomas comparable to the gadolinium-enhanced standard practice? Findings The proposed gadolinium-free diagnosis prediction decision tree for adult-type diffuse gliomas performed well, and gadolinium-enhanced MRI demonstrated only limited improvement in diagnostic accuracy. Clinical relevance Even inexperienced raters effectively classified adult-type diffuse gliomas using the gadolinium-free diagnosis prediction decision tree, which, until further validation, can be used alongside gadolinium-enhanced images to respect standard practice, despite this study showing that gadolinium-enhanced images hardly improved diagnostic accuracy., (© 2024. The Author(s).)

Background: Visually Accessible Rembrandt (Repository for Molecular Brain Neoplasia Data) Images (VASARI) features, a vocabulary to establish reproducible terminology for glioma reporting, have been applied for a decade, but a systematic performance evaluation is lacking., Purpose: Our aim was to conduct a systematic review and meta-analysis of the performance of the VASARI features set for glioma assessment., Data Sources: MEDLINE, Web of Science, EMBASE, and the Cochrane Library were systematically searched until September 26, 2023., Study Selection: Original articles predicting diagnosis, progression, and survival in patients with glioma were included., Data Analysis: The modified Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool was applied to evaluate the risk-of-bias. The meta-analysis used a random effects model and forest plot visualizations, if ≥5 comparable studies with a low or medium risk of bias were provided., Data Synthesis: Thirty-five studies (3304 patients) were included. Risk-of-bias scores were medium ( n  = 33) and low ( n  = 2). Recurring objectives were overall survival ( n  = 18) and isocitrate dehydrogenase mutation ( IDH ; n  = 12) prediction. Progression-free survival was examined in 7 studies. In 4 studies (glioblastoma n  = 2, grade 2/3 glioma n  = 1, grade 3 glioma n  = 1), a significant association was found between progression-free survival and single VASARI features. The single features predicting overall survival with the highest pooled hazard ratios were multifocality (hazard ratio = 1.80; 95%-CI, 1.21-2.67; I 2 = 53%), ependymal invasion (hazard ratio = 1.73; 95% CI, 1.45-2.05; I 2 = 0%), and enhancing tumor crossing the midline (hazard ratio = 2.08; 95% CI, 1.35-3.18; I 2 = 52%). IDH mutation-predicting models combining VASARI features rendered a pooled area under the receiver operating characteristic curve of 0.82 (95% CI, 0.76-0.88) at considerable heterogeneity (I 2 = 100%). Combined input models using VASARI plus clinical and/or radiomics features outperformed single data-type models in all relevant studies ( n  = 17)., Limitations: Studies were heterogeneously designed and often with a small sample size. Several studies used The Cancer Imaging Archive database, with likely overlapping cohorts. The meta-analysis for IDH was limited due to a high study heterogeneity., Conclusions: Some VASARI features perform well in predicting overall survival and IDH mutation status, but combined models outperform single features. More studies with less heterogeneity are needed to increase the evidence level., (© 2024 by American Journal of Neuroradiology.)

Purpose: To create an inventory of image processing pipelines of arterial spin labeling (ASL) and list their main features, and to evaluate the capability, flexibility, and ease of use of publicly available pipelines to guide novice ASL users in selecting their optimal pipeline., Methods: Developers self-assessed their pipelines using a questionnaire developed by the Task Force 1.1 of the ISMRM Open Science Initiative for Perfusion Imaging. Additionally, each publicly available pipeline was evaluated by two independent testers with basic ASL experience using a scoring system created for this purpose., Results: The developers of 21 pipelines filled the questionnaire. Most pipelines are free for noncommercial use (n = 18) and work with the standard NIfTI (Neuroimaging Informatics Technology Initiative) data format (n = 15). All pipelines can process standard 3D single postlabeling delay pseudo-continuous ASL images and primarily differ in their support of advanced sequences and features. The publicly available pipelines (n = 9) were included in the independent testing, all of them being free for noncommercial use. The pipelines, in general, provided a trade-off between ease of use and flexibility for configuring advanced processing options., Conclusion: Although most ASL pipelines can process the common ASL data types, only some (namely, ASLPrep, ASLtbx, BASIL/Quantiphyse, ExploreASL, and MRICloud) are well-documented, publicly available, support multiple ASL types, have a user-friendly interface, and can provide a useful starting point for ASL processing. The choice of an optimal pipeline should be driven by specific data to be processed and user experience, and can be guided by the information provided in this ASL inventory., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Gadolinium-based contrast agents (GBCAs) form the cornerstone of current primary brain tumor MRI protocols at all stages of the patient journey. Though an imperfect measure of tumor grade, GBCAs are repeatedly used for diagnosis and monitoring. In practice, however, radiologists will encounter situations where GBCA injection is not needed or of doubtful benefit. Reducing GBCA administration could improve the patient burden of (repeated) imaging (especially in vulnerable patient groups, such as children), minimize risks of putative side effects, and benefit costs, logistics, and the environmental footprint. On the basis of the current literature, imaging strategies to reduce GBCA exposure for pediatric and adult patients with primary brain tumors will be reviewed. Early postoperative MRI and fixed-interval imaging of gliomas are examples of GBCA exposure with uncertain survival benefits. Half-dose GBCAs for gliomas and T2-weighted imaging alone for meningiomas are among options to reduce GBCA use. While most imaging guidelines recommend using GBCAs at all stages of diagnosis and treatment, non-contrast-enhanced sequences, such as the arterial spin labeling, have shown a great potential. Artificial intelligence methods to generate synthetic postcontrast images from decreased-dose or non-GBCA scans have shown promise to replace GBCA-dependent approaches. This review is focused on pediatric and adult gliomas and meningiomas. Special attention is paid to the quality and real-life applicability of the reviewed literature., (© RSNA, 2024.)

Preoperative clinical magnetic resonance imaging (MRI) protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation or lack thereof. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this first part, we discuss dynamic susceptibility contrast and dynamic contrast-enhanced MRI, arterial spin labeling, diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting. The second part of this review addresses magnetic resonance spectroscopy, chemical exchange saturation transfer, susceptibility-weighted imaging, MRI-PET, MR elastography, and MR-based radiomics applications. Evidence Level: 3 Technical Efficacy: Stage 2., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Preoperative clinical MRI protocols for gliomas, brain tumors with dismal outcomes due to their infiltrative properties, still rely on conventional structural MRI, which does not deliver information on tumor genotype and is limited in the delineation of diffuse gliomas. The GliMR COST action wants to raise awareness about the state of the art of advanced MRI techniques in gliomas and their possible clinical translation. This review describes current methods, limits, and applications of advanced MRI for the preoperative assessment of glioma, summarizing the level of clinical validation of different techniques. In this second part, we review magnetic resonance spectroscopy (MRS), chemical exchange saturation transfer (CEST), susceptibility-weighted imaging (SWI), MRI-PET, MR elastography (MRE), and MR-based radiomics applications. The first part of this review addresses dynamic susceptibility contrast (DSC) and dynamic contrast-enhanced (DCE) MRI, arterial spin labeling (ASL), diffusion-weighted MRI, vessel imaging, and magnetic resonance fingerprinting (MRF). EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review., (© 2023 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Magnetic Resonance Spin TomogrAphy in Time-domain (MR-STAT) can reconstruct whole-brain multi-parametric quantitative maps (eg, T 1 , T 2 ) from a 5-minute MR acquisition. These quantitative maps can be leveraged for synthetization of clinical image contrasts., Purpose: The objective was to assess image quality and overall diagnostic accuracy of synthetic MR-STAT contrasts compared to conventional contrast-weighted images., Study Type: Prospective cross-sectional clinical trial., Population: Fifty participants with a median age of 45 years (range: 21-79 years) consisting of 10 healthy participants and 40 patients with neurological diseases (brain tumor, epilepsy, multiple sclerosis or stroke)., Field Strength/sequence: 3T/Conventional contrast-weighted imaging (T 1 /T 2 weighted, proton density [PD] weighted, and fluid-attenuated inversion recovery [FLAIR]) and a MR-STAT acquisition (2D Cartesian spoiled gradient echo with varying flip angle preceded by a non-selective inversion pulse)., Assessment: Quantitative T 1 , T 2 , and PD maps were computed from the MR-STAT acquisition, from which synthetic contrasts were generated. Three neuroradiologists blinded for image type and disease randomly and independently evaluated synthetic and conventional datasets for image quality and diagnostic accuracy, which was assessed by comparison with the clinically confirmed diagnosis., Statistical Tests: Image quality and consequent acceptability for diagnostic use was assessed with a McNemar's test (one-sided α = 0.025). Wilcoxon signed rank test with a one-sided α = 0.025 and a margin of Δ = 0.5 on the 5-level Likert scale was used to assess non-inferiority., Results: All data sets were similar in acceptability for diagnostic use (≥3 Likert-scale) between techniques (T 1 w:P = 0.105, PDw:P = 1.000, FLAIR:P = 0.564). However, only the synthetic MR-STAT T 2 weighted images were significantly non-inferior to their conventional counterpart; all other synthetic datasets were inferior (T 1 w:P = 0.260, PDw:P = 1.000, FLAIR:P = 1.000). Moreover, true positive/negative rates were similar between techniques (conventional: 88%, MR-STAT: 84%)., Data Conclusion: MR-STAT is a quantitative technique that may provide radiologists with clinically useful synthetic contrast images within substantially reduced scan time., Evidence Level: 1 Technical Efficacy: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To gain insight into how patients with primary brain tumors experience MRI, follow-up protocols, and gadolinium-based contrast agent (GBCA) use., Methods: Primary brain tumor patients answered a survey after their MRI exam. Questions were analyzed to determine trends in patients' experience regarding the scan itself, follow-up frequency, and the use of GBCAs. Subgroup analysis was performed on sex, lesion grade, age, and the number of scans. Subgroup comparison was made using the Pearson chi-square test and the Mann-Whitney U-test for categorical and ordinal questions, respectively., Results: Of the 100 patients, 93 had a histopathologically confirmed diagnosis, and seven were considered to have a slow-growing low-grade tumor after multidisciplinary assessment and follow-up. 61/100 patients were male, with a mean age ± standard deviation of 44 ± 14 years and 46 ± 13 years for the females. Fifty-nine patients had low-grade tumors. Patients consistently underestimated the number of their previous scans. 92% of primary brain tumor patients did not experience the MRI as bothering and 78% would not change the number of follow-up MRIs. 63% of the patients would prefer GBCA-free MRI scans if diagnostically equally accurate. Women found the MRI and receiving intravenous cannulas significantly more uncomfortable than men (p = 0.003). Age, diagnosis, and the number of previous scans had no relevant impact on the patient experience., Conclusion: Patients with primary brain tumors experienced current neuro-oncological MRI practice as positive. Especially women would, however, prefer GBCA-free imaging if diagnostically equally accurate. Patient knowledge of GBCAs was limited, indicating improvable patient information., (© 2023. The Author(s).)

Objectives: Degeneration of the cholinergic basal forebrain nuclei (CBFN) system has been studied extensively in Alzheimer's disease (AD). White matter hyperintensities are a hallmark of aging as well as a common co-morbidity of AD, but their contribution to CBFN degeneration has remained unclear. Therefore, we explored the influence of white matter hyperintensities within cholinergic subcortical-cortical projection pathways on CBFN volumes and regional gray matter volumes in AD and age- and gender-matched controls., Methods: We analyzed magnetic resonance images (MRI) from 42 patients with AD and 87 age- and gender-matched control subjects. We assessed the white matter hyperintensity burden within the cholinergic projection pathways using the Cholinergic Pathways Hyperintensities Scale (CHIPS), and applied probabilistic anatomical maps for the analysis of CBFN volumes, i.e. the Ch1-3 compartment and the Ch4 cell group (nucleus basalis of Meynert), by diffeomorphic anatomical registration using exponentiated lie algebra analysis of voxel-based morphometry. Using multiple linear regression analyses, we explored correlations between regional gray matter volumes and the extent of white matter hyperintensities or CBFN volumes in both groups., Results: In AD, all CBFN volumes were significantly smaller than in controls, and white matter hyperintensity burden within the cholinergic projection pathways was not correlated with CBFN volume. In controls, white matter hyperintensity burden within the cholinergic projection pathways was inversely correlated with CBFN volume when corrected for sex and total intracranial volume, but this correlation was no longer significant after correction for age. Voxel-wise multiple linear regression analyses using threshold-free cluster enhancement revealed that in controls, cholinergic pathway hyperintensities correlated with gray matter loss in perisylvian areas, whereas the were no effects in AD. Moreover, we found that CBFN volumes correlated with distinct regional cortical atrophy patterns in both groups., Conclusion: Our results indicate that white matter hyperintensities and AD pathology contribute independently but additively to the degeneration of cholinergic basal forebrain structures. Whereas AD is primarily associated with CBFN volume loss, cholinergic degeneration associated with white matter hyperintensities appears to involve disruption of cholinergic cortical projection fibers with less pronounced effects on CBFN volumes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Amide proton transfer (APT) imaging is a chemical exchange saturation transfer (CEST) technique offering potential clinical applications such as diagnosis, characterization, and treatment planning and monitoring in glioma patients. While APT-CEST has demonstrated high potential, reproducibility remains underexplored., Purpose: To investigate whether cerebral APT-CEST with clinically feasible scan time is reproducible in healthy tissue and glioma for clinical use at 3 T., Study Type: Prospective, longitudinal., Subjects: Twenty-one healthy volunteers (11 females; mean age ± SD: 39 ± 11 years) and 6 glioma patients (3 females; 50 ± 17 years: 4 glioblastomas, 1 oligodendroglioma, 1 radiologically suspected low-grade glioma)., Field Strength/sequence: 3 T, Turbo Spin Echo - ampling perfection with application optimized contrasts using different flip angle evolution - chemical exchange saturation transfer (TSE SPACE-CEST)., Assessment: APT-CEST measurement reproducibility was assessed within-session (glioma patients, scan session 1; healthy volunteers scan sessions 1, 2, and 3), between-sessions (healthy volunteers scan sessions 1 and 2), and between-days (healthy volunteers, scan sessions 1 and 3). The mean APT CEST values and standard deviation of the within-subject difference (SD diff ) were calculated in whole tumor enclosed by regions of interest (ROIs) in patients, and eight ROIs in healthy volunteers-whole-brain, cortical gray matter, putamen, thalami, orbitofrontal gyri, occipital lobes, central brain-and compared., Statistical Tests: Brown-Forsythe tests and variance component analysis (VCA) were used to assess the reproducibility of ROIs for the three time intervals. Significance was set at P < 0.003 after Bonferroni correction., Results: Intratumoral mean APT CEST was significantly higher than APT CEST in healthy-appearing tissue in patients (0.5 ± 0.46%). The average within-session, between-sessions, and between-days SD diff of healthy control brains was 0.2% and did not differ significantly with each other (0.76 > P > 0.22). The within-session SD diff of whole-brain was 0.2% in both healthy volunteers and patients, and 0.21% in the segmented tumor. VCA showed that within-session factors were the most important (60%) for scanning variance., Data Conclusion: Cerebral APT-CEST imaging may show good scan-rescan reproducibility in healthy tissue and tumors with clinically feasible scan times at 3 T. Short-term measurement effects may be the dominant components for reproducibility., Level of Evidence: 2 TECHNICAL EFFICACY: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objective: High spatial and temporal resolution contrast-enhanced magnetic resonance angiography (MRA) with gadolinium-based contrast agents (GBCAs) at standard dose offers both detailed anatomic information on both arterial and venous vessels and hemodynamic characteristics. Several preclinical and clinical dynamic 3-dimensional (3D) MRA studies that focused on arterial vessels only proposed that high image quality may also be achieved with significantly reduced GBCA doses, calling into question the need to use standard doses. A systematic analysis of GBCA doses and resulting image quality for both arteries and veins has not yet been performed. The purpose of this study was therefore to systematically analyze dose-dependent vascular enhancements in dynamic 3D-MRA of the thoracoabdominal vasculature at 1.5 T in an animal model to determine the optimal contrast agent protocol for optimized vascular assessment., Materials and Methods: The vascular enhancement in thoracoabdominal dynamic 3D-MRA (time-resolved angiography with interleaved stochastic trajectories, TWIST at 1.5 T) was interindividually and intraindividually compared in 5 anesthetized Göttingen minipigs using gadobutrol at the standard dose (0.1 mmol/kg body weight, ie, 0.1 mL/kg) and at reduced doses (0.08, 0.06, 0.04, 0.02 mmol/kg) in a randomized order. All injections were performed at 2 mL/s followed by 20 mL saline. Images were quantitatively analyzed, measuring signal intensities in 5 regions that covered the passage of the GBCA through the body at different representative stages of circulation (pulmonary, arterial, and venous system). The evaluation of GBCA dose-dependent signal intensity changes in the different vascular regions was performed by linear regression analysis.The qualitative image analysis of dynamic 3D-MRA by 3 independent radiologists included the visibility of 25 arterial and venous vessel segments at different stages of GBCA passage. Possible quality losses were statistically tested by comparing image quality ratings at the reduced dose with that of the standard dose using Friedman test followed by Dunn post hoc test for multiple comparison. Significance was stated at P < 0.05., Results: Quantitative analysis revealed shorter time-to-peak intervals and bolus durations in line with decreasing GBCA dose and volume in all vessels. Although the peak signal was almost independent of the administered GBCA dose at the level of the pulmonary trunk, a linear signal decrease in the abdominal aorta ( r2 = 0.96), the renal arteries ( r2 = 0.99), the inferior vena cava ( r2 = 0.99), and the portal vein ( r2 = 0.97) was observed. Cumulative analysis of arterial segments revealed significantly lower image quality at doses below 40% of the standard dose, whereas in venous segments, significantly lower image quality was observed at doses below 60% of the standard dose., Conclusions: In dynamic 3D-MRA at 1.5 T, dose reduction leads to a signal loss that is most pronounced in the venous system and results in significantly lower image quality according to the dose and vessels of interest. Careful dose reduction is thus required according to the specific diagnostic needs. For dynamic 3D-MRA of the arterial and venous system, GBCA doses of at least 60% of the standard dose up to the full dose are preferable, whereas 40% of the standard dose seems feasible if only the arterial system is to be imaged., Competing Interests: Conflicts of interest and sources of funding: The study was performed with support of Bayer AG, Berlin, Germany. The company provided the animals, professionals experienced in handling of the animals including anesthesia, and also the clinical MR scanners that were used in this study. The coauthors G.J. and H.P. are employees of Bayer AG, Berlin, Germany. The coauthors of the manuscript who are employees of either Bayer AG, Berlin, Germany, or with financial, consultant, institutional, and other relationships that might lead to bias or a conflict of interest, had no control over the finalization of the manuscript., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Magnetic resonance-guided focused ultrasound of the ventral intermediate nucleus is a novel incisionless ablative treatment for essential tremor (ET)., Objective: The aim was to study the structural and functional network changes induced by unilateral sonication of the ventral intermediate nucleus in ET., Methods: Fifteen essential tremor patients (66.2 ± 15.4 years) underwent probabilistic tractography and functional magnetic resonance imaging (MRI) during unilateral postural tremor-eliciting tasks using 3-T MRI before, 1 month (N = 15), and 6 months (N = 10) post unilateral sonication., Results: Tractography identified tract-specific alterations within the dentato-thalamo-cortical tract (DTCT) affected by the unilateral lesion after sonication. Relative to the treated hand, task-evoked activation was significantly reduced in contralateral primary sensorimotor cortex and ipsilateral cerebellar lobules IV/V and VI, and vermis. Dynamic causal modeling revealed a significant decrease in excitatory drive from the cerebellum to the contralateral sensorimotor cortex., Conclusions: Thalamic lesions induced by sonication induce specific functional network changes within the DTCT, notably reducing excitatory input to ipsilateral sensorimotor cortex in ET. ©[2022] International Parkinson and Movement Disorder Society. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Arterial spin labeling (ASL) is a non-invasive and cost-effective MRI technique for brain perfusion measurements. While it has developed into a robust technique for scientific and clinical use, its image processing can still be daunting. The 2019 Ann Arbor ISMRM ASL working group established that education is one of the main areas that can accelerate the use of ASL in research and clinical practice. Specifically, the post-acquisition processing of ASL images and their preparation for region-of-interest or voxel-wise statistical analyses is a topic that has not yet received much educational attention. This educational review is aimed at those with an interest in ASL image processing and analysis. We provide summaries of all typical ASL processing steps on both single-subject and group levels. The readers are assumed to have a basic understanding of cerebral perfusion (patho) physiology; a basic level of programming or image analysis is not required. Starting with an introduction of the physiology and MRI technique behind ASL, and how they interact with the image processing, we present an overview of processing pipelines and explain the specific ASL processing steps. Example video and image illustrations of ASL studies of different cases, as well as model calculations, help the reader develop an understanding of which processing steps to check for their own analyses. Some of the educational content can be extrapolated to the processing of other MRI data. We anticipate that this educational review will help accelerate the application of ASL MRI for clinical brain research., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Clement, Petr, Dijsselhof, Padrela, Pasternak, Dolui, Jarutyte, Pinter, Hernandez-Garcia, Jahn, Kuijer, Barkhof, Mutsaerts and Keil.)

Cerebral small vessel disease (CSVD) is associated with changes in the retinal vasculature which can be assessed non-invasively with much higher resolution than the cerebral vasculature. To detect changes at a microvascular level, we used optical coherence tomography angiography which resolves retinal and choroidal vasculature. Participants with CSVD and controls were included. White matter lesions were determined on magnetic resonance imaging (MRI). The retinal and choroidal vasculature were quantified using swept-source optical coherence tomography angiography. Data were analysed using linear regression. We included 30 participants (18 females; patients, n = 20; controls, n = 10) with a mean age of 61 ± 10 years. Patients had a higher mean white matter lesion index and number of lesions than controls (p ≤ 0.002). The intraindividual deviation of choriocapillaris reflectivity differed significantly between age-matched patients (0.234 ± 0.012) and controls (0.247 ± 0.011; p = 0.029). Skeleton density of the deep retinal capillaries was significantly associated with the number of lesions on MRI (β = - 5.3 × 10 8 , 95%-confidence interval [- 10.3 × 10 8 ; - 0.2 × 10 8 ]) when controlling for age. The choroidal microvasculature and the deep retinal vascular plexus, as quantified by optical coherence tomography angiography, are significantly altered in CSVD. The value of these findings in diagnosing or monitoring CSVD need to be assessed in future studies., (© 2022. The Author(s).)

Objective: Summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and highlight the latest bench-to-bedside developments., Methods: Experts in advanced MRI techniques applied to high-grade glioma treatment response assessment convened through a European framework. Current evidence regarding the potential for monitoring biomarkers in adult high-grade glioma is reviewed, and individual modalities of perfusion, permeability, and microstructure imaging are discussed (in Part 1 of two). In Part 2, we discuss modalities related to metabolism and/or chemical composition, appraise the clinic readiness of the individual modalities, and consider post-processing methodologies involving the combination of MRI approaches (multiparametric imaging) or machine learning (radiomics)., Results: High-grade glioma vasculature exhibits increased perfusion, blood volume, and permeability compared with normal brain tissue. Measures of cerebral blood volume derived from dynamic susceptibility contrast-enhanced MRI have consistently provided information about brain tumor growth and response to treatment; it is the most clinically validated advanced technique. Clinical studies have proven the potential of dynamic contrast-enhanced MRI for distinguishing post-treatment related effects from recurrence, but the optimal acquisition protocol, mode of analysis, parameter of highest diagnostic value, and optimal cut-off points remain to be established. Arterial spin labeling techniques do not require the injection of a contrast agent, and repeated measurements of cerebral blood flow can be performed. The absence of potential gadolinium deposition effects allows widespread use in pediatric patients and those with impaired renal function. More data are necessary to establish clinical validity as monitoring biomarkers. Diffusion-weighted imaging, apparent diffusion coefficient analysis, diffusion tensor or kurtosis imaging, intravoxel incoherent motion, and other microstructural modeling approaches also allow treatment response assessment; more robust data are required to validate these alone or when applied to post-processing methodologies., Conclusion: Considerable progress has been made in the development of these monitoring biomarkers. Many techniques are in their infancy, whereas others have generated a larger body of evidence for clinical application., Competing Interests: Author KS has ownership interest in IQ-AI Ltd and financial interest in Imaging Biometrics LLC. Author TB has participated in a speaker’s bureau for AbbVie and Siemens Healthineers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Henriksen, del Mar Álvarez-Torres, Figueiredo, Hangel, Keil, Nechifor, Riemer, Schmainda, Warnert, Wiegers and Booth.)

Objective: To summarize evidence for use of advanced MRI techniques as monitoring biomarkers in the clinic, and to highlight the latest bench-to-bedside developments., Methods: The current evidence regarding the potential for monitoring biomarkers was reviewed and individual modalities of metabolism and/or chemical composition imaging discussed. Perfusion, permeability, and microstructure imaging were similarly analyzed in Part 1 of this two-part review article and are valuable reading as background to this article. We appraise the clinic readiness of all the individual modalities and consider methodologies involving machine learning (radiomics) and the combination of MRI approaches (multiparametric imaging)., Results: The biochemical composition of high-grade gliomas is markedly different from healthy brain tissue. Magnetic resonance spectroscopy allows the simultaneous acquisition of an array of metabolic alterations, with choline-based ratios appearing to be consistently discriminatory in treatment response assessment, although challenges remain despite this being a mature technique. Promising directions relate to ultra-high field strengths, 2-hydroxyglutarate analysis, and the use of non-proton nuclei. Labile protons on endogenous proteins can be selectively targeted with chemical exchange saturation transfer to give high resolution images. The body of evidence for clinical application of amide proton transfer imaging has been building for a decade, but more evidence is required to confirm chemical exchange saturation transfer use as a monitoring biomarker. Multiparametric methodologies, including the incorporation of nuclear medicine techniques, combine probes measuring different tumor properties. Although potentially synergistic, the limitations of each individual modality also can be compounded, particularly in the absence of standardization. Machine learning requires large datasets with high-quality annotation; there is currently low-level evidence for monitoring biomarker clinical application., Conclusion: Advanced MRI techniques show huge promise in treatment response assessment. The clinical readiness analysis highlights that most monitoring biomarkers require standardized international consensus guidelines, with more facilitation regarding technique implementation and reporting in the clinic., Competing Interests: KS: Ownership interest in IQ-AI Ltd and financial interest in Imaging Biometrics LLC. TB speaker’s bureau for AbbVie and Siemens Healthineers. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Booth, Wiegers, Warnert, Schmainda, Riemer, Nechifor, Keil, Hangel, Figueiredo, Álvarez-Torres and Henriksen.)

Cancer therapy for both central nervous system (CNS) and non-CNS tumors has been previously associated with transient and long-term cognitive deterioration, commonly referred to as 'chemo fog'. This therapy-related damage to otherwise normal-appearing brain tissue is reported using post-mortem neuropathological analysis. Although the literature on monitoring therapy effects on structural magnetic resonance imaging (MRI) is well established, such macroscopic structural changes appear relatively late and irreversible. Early quantitative MRI biomarkers of therapy-induced damage would potentially permit taking these treatment side effects into account, paving the way towards a more personalized treatment planning.This systematic review (PROSPERO number 224196) provides an overview of quantitative tomographic imaging methods, potentially identifying the adverse side effects of cancer therapy in normal-appearing brain tissue. Seventy studies were obtained from the MEDLINE and Web of Science databases. Studies reporting changes in normal-appearing brain tissue using MRI, PET, or SPECT quantitative biomarkers, related to radio-, chemo-, immuno-, or hormone therapy for any kind of solid, cystic, or liquid tumor were included. The main findings of the reviewed studies were summarized, providing also the risk of bias of each study assessed using a modified QUADAS-2 tool. For each imaging method, this review provides the methodological background, and the benefits and shortcomings of each method from the imaging perspective. Finally, a set of recommendations is proposed to support future research., (© 2021. The Author(s).)

Purpose: To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma., Methods: 120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters., Results: All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. K trans , k ep and v e were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in K trans (p = 0.007) and v e (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones., Conclusion: The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups., (© 2021. The Author(s).)

Despite effective combination anti-retroviral therapy (cART), perinatally HIV infected (PHIV) adolescents still experience cognitive complications. We previously reported higher cerebral blood flow (CBF) in basal ganglia and white matter (WM) in PHIV children compared to matched controls. In healthy children CBF is associated with cognitive domains. To determine longitudinal changes in CBF and its impact on cognitive complications, we measured CBF-using arterial spin labeling-in 21 PHIV adolescents and 23 controls matched for age, sex and socio-economic status twice with a mean follow-up of 4.6 years. We explored associations between CBF changes and WM micro- and macrostructural markers and cognitive domains using linear mixed models. The median age at follow-up was comparable between PHIV adolescents 17.4y (IQR:15.3-20.7) and controls 16.2y (IQR:15.6-19.1). At baseline, PHIV had higher CBF in the caudate nucleus and putamen. CBF development was comparable in gray matter (GM), WM and subcortical regions in both groups. In our cohort, we found that over time an increase of GM CBF was associated with an increase of visual motor function ( p = 0.043) and executive function ( p = 0.045). Increase of CBF in the caudate nucleus, putamen and thalamus was associated with an increase processing speed ( p = 0.033; 0.036; 0.003 respectively) and visual motor function ( p = 0.023; 0.045; 0.003 respectively). CBF development is relatively normal in PHIV adolescents on cART. CBF decline is associated with cognitive impairment, irrespective of HIV status.

Introduction: The ventral intermediate nucleus of the thalamus (VIM) is an important relay station receiving cerebellar and pallidal fiber tracts. Data on structural visualization of the VIM however is limited and uncertainty prevails to what extent lesional approaches to treat tremor affect the VIM itself or passing tracts. The aim of the study was to analyze the localization of individual lesions with respect to the VIM and the cerebello-thalamic tract (CTT)., Methods: We employed ultrahigh resolution (7 Tesla) MRI to delineate the VIM and performed 3 T-DTI-imaging pre- and post-interventional in seven ET patients undergoing transcranial magnetic resonance guided focused ultrasound (tcMRgFUS). Tremor improvement was measured using a modified subscore of the Clinical Rating Scale for Tremor., Results: All subjects showed substantial tremor improvement (88.5%, range 80.7%-94,8%) after tcMRgFUS. We found only a minor overlap of the lesions with the VIM (4%, range 1%-7%) but a larger overlap with the CTT (43%, range 23%-60%) in all subjects., Conclusions: Lesions within the CTT rather than the VIM seem to drive the tremorlytic response and clinical improvement in tcMRgFUS., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Quantitative MRI (qMRI) methods provide versatile neuroradiological applications and are a hot topic in research. The degree of their clinical implementation is however barely known. This survey was created to illuminate which and how qMRI techniques are currently applied across Europe., Methods: In total, 4753 neuroradiologists from 27 countries received an online questionnaire. Demographic and professional data, experience with qMRI techniques in the brain and head and neck, usage, reasons for/against application, and knowledge of the QIBA and EIBALL initiatives were assessed., Results: Two hundred seventy-two responders in 23 countries used the following techniques clinically (mean values in %): DWI (82.0%, n = 223), DSC (67.3%, n = 183), MRS (64.3%, n = 175), DCE (43.4%, n = 118), BOLD-fMRI (42.6%, n = 116), ASL (37.5%, n = 102), fat quantification (25.0%, n = 68), T2 mapping (16.9%, n = 46), T1 mapping (15.1%, n = 41), PET-MRI (11.8%, n = 32), IVIM (5.5%, n = 15), APT-CEST (4.8%, n = 13), and DKI (3.3%, n = 9). The most frequent usage indications for any qMRI technique were tissue differentiation (82.4%, n = 224) and oncological monitoring (72.8%, n = 198). Usage differed between countries, e.g. ASL: Germany (n = 13/63; 20.6%) vs. France (n = 31/40; 77.5%). Neuroradiologists endorsed the use of qMRI because of an improved diagnostic accuracy (89.3%, n = 243), but 50.0% (n = 136) are in need of better technology, 34.9% (n = 95) wish for more communication, and 31.3% need help with result interpretation/generation (n = 85). QIBA and EIBALL were not well known (12.5%, n = 34, and 11.0%, n = 30)., Conclusions: The clinical implementation of qMRI methods is highly variable. Beyond the aspect of readiness for clinical use, better availability of support and a wider dissemination of guidelines could catalyse a broader implementation., Key Points: • Neuroradiologists endorse the use of qMRI techniques as they subjectively improve diagnostic accuracy. • Clinical implementation is highly variable between countries, techniques, and indications. • The use of advanced imaging could be promoted through an increase in technical support and training of both doctors and technicians., (© 2021. The Author(s).)

Spatial normalization is an important step for group image processing and evaluation of mean brain perfusion in anatomical regions using arterial spin labeling (ASL) MRI and is typically performed via high-resolution structural brain scans. However, structural segmentation and/or spatial normalization to standard space is complicated when gray-white matter contrast in structural images is low due to ongoing myelination in newborns and infants. This problem is of particularly clinical relevance for imaging infants with inborn or acquired disorders that impair normal brain development. We investigated whether the ASL MRI perfusion contrast is a viable alternative for spatial normalization, using a pseudo-continuous ASL acquired using a 1.5 T MRI unit (GE Healthcare). Four approaches have been compared: (1) using the structural image contrast, or perfusion contrast with (2) rigid, (3) affine, and (4) nonlinear transformations - in 16 healthy controls [median age 0.83 years, inter-quartile range (IQR) ± 0.56] and 36 trigonocephaly patients (median age 0.50 years, IQR ± 0.30) - a non-syndromic type of craniosynostosis. Performance was compared quantitatively using the real-valued Tanimoto coefficient (TC), visually by three blinded readers, and eventually by the impact on regional cerebral blood flow (CBF) values. For both patients and controls, nonlinear registration using perfusion contrast showed the highest TC, at 17.51 (CI 6.66-49.38) times more likely to have a higher rating and 17.45-18.88 ml/100 g/min higher CBF compared with the standard normalization. Using perfusion-based contrast improved spatial normalization compared with the use of structural images, significantly affected the regional CBF, and may open up new possibilities for future large pediatric ASL brain studies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 de Planque, Mutsaerts, Keil, Erler, Dremmen, Mathijssen and Petr.)

Objective: Transsylvian selective amygdalo-hippocampectomy (tsSAHE) represents a generally recognized surgical procedure for drug-resistant mesial temporal lobe epilepsy (mTLE). Although postoperative seizure freedom can be achieved in about 70% of tsSAHE, there is a considerable amount of patients with persisting postoperative seizures. This might partly be explained by differing extents of resection of various tsSAHE target volumes. In this study we analyzed the resected proportions of hippocampus, amygdala as well as piriform cortex in regard of postoperative seizure outcome., Methods: Between 2012 and 2017, 82 of 103 patients with mTLE who underwent tsSAHE at the authors' institution were included in the analysis. Resected proportions of hippocampus, amygdala and temporal piriform cortex as target structures of tsSAHE were volumetrically assessed and stratified according to favorable (International League Against Epilepsy (ILAE) class 1) and unfavorable (ILAE class 2-6) seizure outcome., Results: Patients with favorable seizure outcome revealed a significantly larger proportion of resected temporal piriform cortex volumes compared to patients with unfavorable seizure outcome (median resected proportional volumes were 51% (IQR 42-61) versus (vs.) 13 (IQR 11-18), P = 0.0001). Resected proportions of hippocampus and amygdala did not significantly differ for these groups (hippocampus: 81% (IQR 73-88) vs. 80% (IQR 74-92) (P = 0.7); amygdala: 100% (IQR 100-100) vs. 100% (IQR 100-100) (P = 0.7))., Interpretation: These results strongly suggest temporal piriform cortex to constitute a key target resection volume to achieve seizure freedom following tsSAHE., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Purpose: There is an annual incidence of 50,000 glioma cases in Europe. The optimal treatment strategy is highly personalised, depending on tumour type, grade, spatial localization, and the degree of tissue infiltration. In research settings, advanced magnetic resonance imaging (MRI) has shown great promise as a tool to inform personalised treatment decisions. However, the use of advanced MRI in clinical practice remains scarce due to the downstream effects of siloed glioma imaging research with limited representation of MRI specialists in established consortia; and the associated lack of available tools and expertise in clinical settings. These shortcomings delay the translation of scientific breakthroughs into novel treatment strategy. As a response we have developed the network "Glioma MR Imaging 2.0" (GliMR) which we present in this article., Methods: GliMR aims to build a pan-European and multidisciplinary network of experts and accelerate the use of advanced MRI in glioma beyond the current "state-of-the-art" in glioma imaging. The Action Glioma MR Imaging 2.0 (GliMR) was granted funding by the European Cooperation in Science and Technology (COST) in June 2019., Results: GliMR's first grant period ran from September 2019 to April 2020, during which several meetings were held and projects were initiated, such as reviewing the current knowledge on advanced MRI; developing a General Data Protection Regulation (GDPR) compliant consent form; and setting up the website., Conclusion: The Action overcomes the pre-existing limitations of glioma research and is funded until September 2023. New members will be accepted during its entire duration., Competing Interests: Conflict of interestMarion Smits is ‘speaker honoraria’ from GE Healthcare, for which honoraria are paid to the author’s institution. Vera C. Keil is an invited paid lecturer for Philips healthcare in Germany and Switzerland., (© The Author(s) 2020.)

Parkinson's disease (PD) affects more than six million people, but reliable MRI biomarkers with which to diagnose patients have not been established. Magnetic resonance fingerprinting (MRF) is a recent quantitative technique that can provide relaxometric maps from a single sequence. The purpose of this study is to assess the potential of MRF to identify PD in patients and their disease severity, as well as to evaluate comfort during MRF. Twenty-five PD patients and 25 matching controls underwent 3 T MRI, including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 maps were generated by voxel-wise matching the measured MRF signal to a precomputed dictionary. All participants also received standard inversion recovery T1 and multi-echo T2 mapping. An ROI-based analysis of relaxation times was performed. Differences between patients and controls as well as techniques were determined by logistic regression, Spearman correlation and t-test. Patients were asked to estimate the subjective comfort of the MRF sequence. Both MRF-based T1 and T2 mapping discriminated patients from controls: T1 relaxation times differed most in cortical grey matter (PD 1337 ± 38 vs. control 1386 ± 37 ms; mean ± SD; P = .0001) and, in combination with normal-appearing white matter, enabled correct discrimination in 85.7% of cases (sensitivity 83.3%; specificity 88.0%; receiver-operating characteristic [ROC]) area under the curve [AUC] 0.87), while for T2 mapping the left putamen was the strongest classifier (40.54 ± 6.28 vs. 34.17 ± 4.96 ms; P = .0001), enabling differentiation of groups in 84.0% of all cases (sensitivity 80.0%; specificity 88.0%; ROC AUC 0.87). Relaxation time differences were not associated with disease severity. Standard mapping techniques generated significantly different relaxation time values and identified other structures as different between groups other than MRF. Twenty-three out of 25 PD patients preferred the MRF examination instead of a standard MRI. MRF-based mapping can identify PD patients with good comfort but needs further assessment regarding disease severity identification and its potential for comparability with standard mapping technique results., (© 2020 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.)

Purpose: Magnetic resonance-guided focused ultrasound (MRgFUS) systems are increasingly used to non-invasively treat tremor; consensus on imaging follow-up is poor in these patients. This study aims to elucidate how MRgFUS lesions evolve for a radiological readership with regard to clinical outcome., Methods: MRgFUS-induced lesions and oedema were retrospectively evaluated based on DWI, SWI, T2-weighted and T1-weighted 3-T MRI data acquired 30 min and 3, 30 and 180 days after MRgFUS (n = 9 essential tremor, n = 1 Parkinson's patients). Lesions were assessed volumetrically, visually and by ADC measurements and compared with clinical effects using non-parametric testing., Results: Thirty minutes after treatment, all lesions could be identified on T2-weighted images. Immediate oedema was rare (n = 1). Lesion volume as well as oedema reached a maximum on day 3 with a mean lesion size of 0.4 ± 0.2 cm 3 and an oedema volume 3.7 ± 1.2 times the lesion volume. On day 3, a distinct diffusion-restricted rim was noted that corresponded well with SWI. Lesion shrinkage after day 3 was observed in all sequences. Lesions were no longer detectable on DWI in n = 7/10, on T2-weighted images in n = 4/10 and on T1-weighted images in n = 4/10 on day 180. No infarcts or haemorrhage were observed. There was no correlation between lesion size and initial motor skill improvement (p = 0.99). Tremor reduction dynamics correlated strongly with lesion shrinkage between days 3 and 180 (p = 0.01, R = 0.76)., Conclusion: In conclusion, cerebral MRgFUS lesions variably shrink over months. SWI is the sequence of choice to identify lesions after 6 months. Lesion volume is arguably associated with intermediate-term outcome.

The hot cross bun (HCB) sign describes cruciform-shaped T2-weighted hyperintensities of pontocerebellar fibers within the pons and is a typical, but not specific imaging hallmark of the cerebellar variant of multiple system atrophy (MSA-C). We report a case of a 51-year-old woman who was first diagnosed with MSA-C based on progressive cerebellar ataxia, the HCB sign and T2-weighted hyperintensities in middle cerebellar peduncles on MRI. However, further diagnostic work-up revealed positive anti-amphiphysin antibodies in blood and cerebrospinal fluid and subsequently breast cancer. This report of a paraneoplastic rhombencephalitis which initially mimicked MSA-C imaging features stresses the importance of considering immune-mediated rhombencephalitis as differential diagnosis in cases of progressive cerebellar ataxia and the HCB sign on T2-weighted MRI, especially in the absence of pontocerebellar atrophy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Several very rare forms of dementia are associated with characteristic focal atrophy predominantly of the frontal and/or temporal lobes and currently lack imaging solutions to monitor disease. Magnetic resonance fingerprinting (MRF) is a recently developed technique providing quantitative relaxivity maps and images with various tissue contrasts out of a single sequence acquisition. This pilot study explores the utility of MRF-based T1 and T2 mapping to discover focal differences in relaxation times between patients with frontotemporal lobe degenerative dementia and healthy controls. 8 patients and 30 healthy controls underwent a 3 T MRI including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 relaxation maps were generated based on an extended phase graphs algorithm-founded dictionary involving inner product pattern matching. A region of interest (ROI)-based analysis of T1 and T2 relaxation times was performed with FSL and ITK-SNAP. Depending on the brain region analyzed, T1 relaxation times were up to 10.28% longer in patients than in controls reaching significant differences in cortical gray matter (P = .047) and global white matter (P = .023) as well as in both hippocampi (P = .001 left; P = .027 right). T2 relaxation times were similarly longer in the hippocampus by up to 19.18% in patients compared with controls. The clinically most affected patient had the most control-deviant relaxation times. There was a strong correlation of T1 relaxation time in the amygdala with duration of the clinically manifest disease (Spearman Rho = .94; P = .001) and of T1 relaxation times in the left hippocampus with disease severity (Rho = .90, P = .002). In conclusion, MRF-based relaxometry is a promising and time-saving new MRI tool to study focal cerebral alterations and identify patients with frontotemporal lobe degeneration. To validate the results of this pilot study, MRF is worth further exploration as a diagnostic tool in neurodegenerative diseases., (© 2019 John Wiley & Sons, Ltd.)

Objective: Supra-total glioblastoma resection has gained growing attention with regard to superior long-term disease control. However, aggressive onco-surgical approaches-geared beyond conventional gross total resections (GTR)-are limited by the impairment of adjacent eloquent areas at risk that may entail severe postoperative functional morbidity. Against this backdrop we analyzed our institutional database with regard to potential survival benefits of anterior temporal lobectomy as a paradigm for supra-total resection in patients with precisely temporal-located, non-eloquent glioblastoma., Methods: Between 2012 and 2017, 38 patients with isolated temporal glioblastoma underwent GTR or temporal lobectomy at the authors' institution. Both groups of differing resection modalities were compared with regard to postoperative Karnofsky performance score (KPS), progression-free survival (PFS), and overall survival (OS)., Results: Patients with temporal lobectomy exhibited significantly superior median KPS at the 12 months follow-up compared to the GTR group (median KPS of 80 vs. 60, p = 0.04). Temporal lobectomy was associated with significantly prolonged PFS (p = 0.005) and OS (p = 0.002) coming up to 15 months (95% CI 9.7-22.1) and 23 months (95% CI 14.8-34.5) compared to 7 months (95% CI 3.3-8.3) and 11 months (95% CI 9.2-17.9) for the GTR group. Multivariate analysis revealed temporal lobectomy as the only predictor for both superior PFS (p = 0.037, OR 7.3, 95% CI 1.1-47.4) and OS (p = 0.04, OR 7.8, 95% CI 1.1-55.2)., Conclusions: These results strongly suggest temporal lobectomy as an aggressive supra-total resection policy to constitute the surgical modality of choice for isolated temporal-located glioblastoma.

Heterozygous activating mutations in platelet-derived growth factor receptor B (PDGFRB) have been recently identified as a cause of autosomal-dominant infantile myofibromatosis. We describe a 36-year-old man with PDGFRB c.1681C>T (p.R561C) mutation. Upon progressive disease, the patient received treatment with imatinib and showed a remarkable response with remission of multiple lesions after 12 months. This is the first report of an adult patient with PDGFRB c.1681C>T mutation treated with imatinib., (© 2019 Wiley Periodicals, Inc.)

Objective: To investigate the structural brain abnormalities and their diagnostic accuracy through qualitative and quantitative analysis in term born and very preterm birth or with very low birth weight (VP/VLBW) adults., Methods: We analyzed 3-T MRIs acquired in 2011-2013 from 67 adults (27 term born controls, mean age 26.4 years, 8 females; 40 VP/VLBWs, mean age 26.6 years, 16 females). We compared automatic segmentations of the white matter, deep gray matter and cortical gray matter, manual corpus callosum measurements and visual ratings of the ventricles and white matter with t tests, logistic regression, and receiver operator characteristic (ROC) curves., Results: Automatic segmentation correctly classified 84% of cases; visual ratings correctly classified 63%. Quantitative volumetry based on automatic segmentation revealed higher ventricular volume, lower posterior corpus callosum, and deep gray matter volumes in VP/VLBW subjects compared to controls (p < 0.01). Visual rating and manual measurement revealed a thinner corpus callosum in VP/VLBW adults (p = 0.04) and deformed lateral ventricles (p = 0.03) and tendency towards more "dirty" white matter (p = 0.06). Automatic/manual measures combined with visual ratings correctly classified 87% of cases. Stepwise logistic regression identified three independent features that correctly classify 81% of cases: ventricular volume, deep gray matter volume, and white matter aspect., Conclusion: Enlarged and deformed lateral ventricles, thinner corpus callosum, and "dirty" white matter are prevalent in preterm born adults. Their visual evaluation has low diagnostic accuracy. Automatic volume quantification is more accurate but time consuming. It may be useful to ask for prematurity before initiating further diagnostics in subjects with these alterations., Key Points: • Our study confirms prior reports showing that structural brain abnormalities related to preterm birth persist into adulthood. • In the clinical practice, if large and deformed lateral ventricles, small and thin corpus callosum, and "dirty" white matter are visible on MRI, ask for prematurity before considering other diagnoses. • Although prevalent, visual findings have low accuracy; adding automatic segmentation of lateral ventricles and deep gray matter nuclei improves the diagnostic accuracy.

Background: There is an urgent need for more effective therapies for glioblastoma. Data from a previous unrandomised phase 2 trial suggested that lomustine-temozolomide plus radiotherapy might be superior to temozolomide chemoradiotherapy in newly diagnosed glioblastoma with methylation of the MGMT promoter. In the CeTeG/NOA-09 trial, we aimed to further investigate the effect of lomustine-temozolomide therapy in the setting of a randomised phase 3 trial., Methods: In this open-label, randomised, phase 3 trial, we enrolled patients from 17 German university hospitals who were aged 18-70 years, with newly diagnosed glioblastoma with methylated MGMT promoter, and a Karnofsky Performance Score of 70% and higher. Patients were randomly assigned (1:1) with a predefined SAS-generated randomisation list to standard temozolomide chemoradiotherapy (75 mg/m 2 per day concomitant to radiotherapy [59-60 Gy] followed by six courses of temozolomide 150-200 mg/m 2 per day on the first 5 days of the 4-week course) or to up to six courses of lomustine (100 mg/m 2 on day 1) plus temozolomide (100-200 mg/m 2 per day on days 2-6 of the 6-week course) in addition to radiotherapy (59-60 Gy). Because of the different schedules, patients and physicians were not masked to treatment groups. The primary endpoint was overall survival in the modified intention-to-treat population, comprising all randomly assigned patients who started their allocated chemotherapy. The prespecified test for overall survival differences was a log-rank test stratified for centre and recursive partitioning analysis class. The trial is registered with ClinicalTrials.gov, number NCT01149109., Findings: Between June 17, 2011, and April 8, 2014, 141 patients were randomly assigned to the treatment groups; 129 patients (63 in the temozolomide and 66 in the lomustine-temozolomide group) constituted the modified intention-to-treat population. Median overall survival was improved from 31·4 months (95% CI 27·7-47·1) with temozolomide to 48·1 months (32·6 months-not assessable) with lomustine-temozolomide (hazard ratio [HR] 0·60, 95% CI 0·35-1·03; p=0·0492 for log-rank analysis). A significant overall survival difference between groups was also found in a secondary analysis of the intention-to-treat population (n=141, HR 0·60, 95% CI 0·35-1·03; p=0·0432 for log-rank analysis). Adverse events of grade 3 or higher were observed in 32 (51%) of 63 patients in the temozolomide group and 39 (59%) of 66 patients in the lomustine-temozolomide group. There were no treatment-related deaths., Interpretation: Our results suggest that lomustine-temozolomide chemotherapy might improve survival compared with temozolomide standard therapy in patients with newly diagnosed glioblastoma with methylated MGMT promoter. The findings should be interpreted with caution, owing to the small size of the trial., Funding: German Federal Ministry of Education and Research., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Arterial spin labeling is a noninvasive, non-gadolinium-dependent magnetic resonance imaging (MRI) technique to assess cerebral blood flow. It provides insight into both tissue metabolic activity and vascular supply. Because of its non-sensitivity toward blood-brain barrier leakage, arterial spin labeling is also more accurate in cerebral blood flow quantification than gadolinium-dependent methods. The aim of this pictorial essay is to promote the application of arterial spin labeling in pediatric neuroradiology. The authors provide information on artifacts and pitfalls as well as numerous fields of application based on pediatric cases.

Background and Purpose: Experienced freedivers can endure prolonged breath-holds despite severe hypoxemia and are therefore ideal subjects to study apnea-induced cerebrovascular reactivity. This multiparametric study investigated CBF, the spatial coefficient of variation as a correlate of arterial transit time and brain metabolism, dynamics during prolonged apnea., Materials and Methods: Fifteen male freedivers (age range, 20-64 years; cumulative previous prolonged breath-holds >2 minutes and 30 seconds: 4-79,200) underwent repetitive 3T pseudocontinuous arterial spin-labeling and 31 P-/ 1 H-MR spectroscopy before, during, and after a 5-minute breath-hold (split into early and late phases) and gave temporally matching venous blood gas samples. Correlation of temporal and regional cerebrovascular reactivity to blood gases and cumulative previous breath-holds of >2 minutes and 30 seconds in a lifetime was assessed., Results: The spatial coefficient of variation of CBF (by arterial spin-labeling) decreased during the early breath-hold phase (-30.0%, P = .002), whereas CBF remained almost stable during this phase and increased in the late phase (+51.8%, P = .001). CBF differed between the anterior and the posterior circulation during all phases (eg, during late breath-hold: MCA, 57.3 ± 14.2 versus posterior cerebral artery, 42.7 ± 10.8 mL/100 g/min; P = .001). There was an association between breath-hold experience and lower CBF (1000 previous breath-holds reduced WM CBF by 0.6 mL/100 g/min; 95% CI, 0.15-1.1 mL/100 g/min; P = .01). While breath-hold caused peripheral lactate rise (+18.5%) and hypoxemia (oxygen saturation, -24.0%), cerebral lactate and adenosine diphosphate remained within physiologic ranges despite early signs of oxidative stress [-6.4% phosphocreatine / (adenosine triphosphate + adenosine diphosphate); P = .02]., Conclusions: This study revealed that the cerebral energy metabolism of trained freedivers withstands severe hypoxic hypercarbia in prolonged breath-hold due to a complex cerebrovascular hemodynamic response., (© 2018 by American Journal of Neuroradiology.)

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Purpose: Quantitative and qualitative analysis of gadopentetate dimeglumine (GD) versus standard-dose (sGb) and half-dose (hGb) gadobutrol in thoracoabdominal time-resolved contrast-enhanced magnetic resonance angiography (4D-MRA) with dynamic computed tomography (dCT) as the quantitative reference in minipigs., Materials and Methods: 7 anesthetized Goettingen minipigs received thoracoabdominal dCT (0.37 s rotation time) and transverse 4D-MRA (0.3 s/dynamic frame;) using sGb and hGb. 8 other minipigs received coronal 4D-MRA (1.3 s/dynamic frame; sGb, hGb, SGD). dCT attenuation levels were converted into absolute gadolinium concentrations and compared to 4D-MRA peak signal intensities (SI). Bolus lengths were quantified by full width at half maximum (FWHM) measurements. After this comparison of dose effects on SI in transverse 4D-MRA, coronal 4D-MRAs were analyzed regarding both quantitative and qualitative parameters., Results: In dCT (transverse 4D-MRA) hGb showed 39.0 % (14.5 %) lower arterial peak gadolinium concentrations (peak SIs) and 20.6 % (33.8 %) shorter FWHM compared to sGb. The difference was due to peak plateaus or reversals in 4D-MRA in 5/7 animals. While sGb led to the highest peak SIs, image quality ratings of arteries were rated similarly high with all contrast agent protocols despite a slightly higher SI with sGb. In contrast, venous peak SIs and image quality ratings were significantly higher when using sGb., Conclusion: Peak Gd concentrations and 4D-MRA peak SIs are highest with sGB. These differences are most evident in the venous phase leading to superior image quality in multi-phase 4D-MRA., Key Points: · Standard-dose gadobutrol offers high vascular gadolinium concentrations and 4D-MRA peak signals.. · Absolute vascular gadolinium concentrations and 4D-MRA peak signal intensities at 3 T diverge.. · Peak plateaus or reversals cause decreased arterial 4D-MRA peak signals at 3 T.. · Arterial image quality is rated similarly high using different contrast agent protocols.. · Venous vessel visibility in 4D-MRA is significantly better using standard dose gadobutrol.., Citation Format: · Hadizadeh DR, Keil VC, Jost G et al. Contrast Media in Time-Resolved MRA at 3T: A Systematic Quantitative and Qualitative Analysis of Concentration and Dose Effects on Image Parameters in Minipigs. Fortschr Röntgenstr 2018; 190: 747 - 757., Competing Interests: The authors of this manuscript declare links to the following companies: Bayer AG, Philips Technology GmbH, Innovative Technologies, Bracco AG, GE, Philips Healthcare and Sirtex Medical. This study was conducted with the support of Bayer, AG, Berlin. The company provided the animals, their caregivers, the anesthetists and the tomographers to carry out the experiments. The co-authors G.J. and H.P. are employed by this company. The co-author M.W. is an employee of Philips Technologie GmbH Innovative Technologies, Research Laboratories, Aachen, and helped with the data analysis. The co-author W.A.W. has held lectures in the past for Bayer AG, Bracco AG, GE, Philips Healthcare and Sirtex Medical. Co-authors of the manuscript who are employees of Bayer AG, Berlin, or Philips Technologie GmbH, Aachen, and who may have a potential financial interest in the results of this study, had no control over the final version of this manuscript., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background and Purpose: Kinetic parameters of T1-weighted dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are considered to be influenced by microvessel environment. This study was performed to explore the extent of this association for meningiomas., Materials and Methods: DCE-MRI kinetic parameters (contrast agent transfer constants K trans and k ep , volume fractions v p and v e ) were determined in pre-operative 3T MRI of meningioma patients for later biopsy sites (19 patients; 15 WHO I o , no previous radiation, and 4 WHO III o pre-radiated recurrent tumors). Sixty-three navigated biopsies were consecutively retrieved. Biopsies were immunohistochemically investigated with endothelial marker CD34 and VEGF antibodies, stratified in a total of 4383 analysis units and computationally assessed for VEGF expression and vascular parameters (vessel density, vessel quantity, vascular fraction within tissue [vascular area ratio], vessel wall thickness). Derivability of kinetic parameters from VEGF expression or microvascularization was determined by mixed linear regression analysis. Tissue kinetic and microvascular parameters were tested for their capacity to identify the radiation status in a subanalysis., Results: Kinetic parameters were neither significantly related to the corresponding microvascular parameters nor to tissue VEGF expression. There was no significant association between microvessel density and its presumed correlate v p (P=0.07). The subgroup analysis of high-grade radiated meningiomas showed a significantly reduced microvascular density (AUC 0.91; P<0.0001) and smaller total vascular fraction (AUC 0.73; P=0.01)., Conclusions: In meningioma, DCE-MRI kinetic parameters neither allow for a reliable prediction of tumor microvascularization, nor for a prediction of VEGF expression. Kinetic parameters seem to be determined from different independent factors., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Purpose: Magnetic resonance (MR) imaging biomarkers can assist in the non-invasive assessment of the genetic status in glioblastomas (GBMs). Telomerase reverse transcriptase (TERT) promoter mutations are associated with a negative prognosis. This study was performed to identify MR imaging biomarkers to forecast the TERT mutation status., Methods: Pre-operative MRIs of 64/67 genetically confirmed primary GBM patients (51/67 TERT-mutated with rs2853669 polymorphism) were analyzed according to Visually AcceSAble Rembrandt Images (VASARI) ( https://wiki.cancerimagingarchive.net/display/Public/VASARI+Research+Project ) imaging criteria by three radiological raters. TERT mutation and O 6 -methylguanine-DNA methyltransferase (MGMT) hypermethylation data were obtained through direct and pyrosequencing as described in a previous study. Clinical data were derived from a prospectively maintained electronic database. Associations of potential imaging biomarkers and genetic status were assessed by Fisher and Mann-Whitney U tests and stepwise linear regression., Results: No imaging biomarkers could be identified to predict TERT mutational status (alone or in conjunction with TERT promoter polymorphism rs2853669 AA-allele). TERT promoter mutations were more common in patients with tumor-associated seizures as first symptom (26/30 vs. 25/37, p = 0.07); these showed significantly smaller tumors [13.1 (9.0-19.0) vs. 24.0 (16.6-37.5) all cm 3 ; p = 0.007] and prolonged median overall survival [17.0 (11.5-28.0) vs. 9.0 (4.0-12.0) all months; p = 0.02]. TERT-mutated GBMs were underrepresented in the extended angularis region (p = 0.03), whereas MGMT-methylated GBMs were overrepresented in the corpus callosum (p = 0.03) and underrepresented temporomesially (p = 0.01)., Conclusion: Imaging biomarkers for prediction of TERT mutation status remain weak and cannot be derived from the VASARI protocol. Tumor-associated seizures are less common in TERT mutated glioblastomas.

Background and Purpose: The occurrence of medulloblastomas in adults is rare; nevertheless, these tumors can be subdivided into genetic and histologic entities each having distinct prognoses. This study aimed to identify MR imaging biomarkers to classify these entities and to uncover differences in MR imaging biomarkers identified in pediatric medulloblastomas., Materials and Methods: Eligible preoperative MRIs from 28 patients (11 women; 22-53 years of age) of the Multicenter Pilot-study for the Therapy of Medulloblastoma of Adults (NOA-7) cohort were assessed by 3 experienced neuroradiologists. Lesions and perifocal edema were volumetrized and multiparametrically evaluated for classic morphologic characteristics, location, hydrocephalus, and Chang criteria. To identify MR imaging biomarkers, we correlated genetic entities sonic hedgehog ( SHH ) TP53 wild type, wingless ( WNT ), and non -WNT/ non -SHH medulloblastomas (in adults, Group 4), and histologic entities were correlated with the imaging criteria. These MR imaging biomarkers were compared with corresponding data from a pediatric study., Results: There were 19 SHH TP53 wild type (69%), 4 WNT -activated (14%), and 5 Group 4 (17%) medulloblastomas. Six potential MR imaging biomarkers were identified, 3 of which, hydrocephalus ( P = .03), intraventricular macrometastases ( P = .02), and hemorrhage ( P = .04), when combined, could identify WNT medulloblastoma with 100% sensitivity and 88.3% specificity (95% CI, 39.8%-100.0% and 62.6%-95.3%). WNT -activated nuclear β-catenin accumulating medulloblastomas were smaller than the other entities (95% CI, 5.2-22.3 cm 3 versus 35.1-47.6 cm 3 ; P = .03). Hemorrhage was exclusively present in non -WNT/ non -SHH medulloblastomas ( P = .04; n = 2/5). MR imaging biomarkers were all discordant from those identified in the pediatric cohort. Desmoplastic/nodular medulloblastomas were more rarely in contact with the fourth ventricle (4/15 versus 7/13; P = .04)., Conclusions: MR imaging biomarkers can help distinguish histologic and genetic medulloblastoma entities in adults and appear to be different from those identified in children., (© 2017 by American Journal of Neuroradiology.)

Purpose: To investigate the effect of the choice of the curve-fitting model on the perfusion fraction (f IVIM ) with regard to tissue type characterization, correlation with microvascular anatomy, and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters. Several curve-fitting models coexist in intravoxel incoherent motion (IVIM) MRI to derive the (f IVIM )., Materials and Methods: In all, 29 patients with brain lesions (12 gliomas, 11 meningiomas, three metastases, two gliotic scars, one multiple sclerosis) underwent IVIM-MRI (32 b-values, 0 to 2000 s/mm 2 ) at 3T. f IVIM was determined by classic monoexponential, biexponential, and a novel nonnegative least squares (NNLS) fitting in 352 regions of interest (lesion-containing and normal-appearing tissue) and tested their correlation with DCE-MRI kinetic parameters and microvascular anatomy derived from 57 region of interest (ROI)-based biopsies and their capacities to differentiate histologically different lesions., Results: f IVIM differed significantly between all three models and all tissue types (monoexponential confidence interval in percent [CI 3.4-3.8]; biexponential [CI 11.21-12.45]; NNLS [CI 2.06-2.60]; all P < 0.001). For all models an increase in f IVIM was associated with a shift to larger vessels and higher vessel area / tissue area ratio (regression coefficient 0.07-0.52; P = 0.04-0.001). Correlation with kinetic parameters derived from DCE-MRI was usually not significant. Only biexponential fitting allowed differentiation of both gliosis from edema and high- from low-grade glioma (both P < 0.001)., Conclusion: The curve-fitting model has an important impact on f IVIM and its capacity to differentiate tissues. f IVIM may possibly be used to assess microvascular anatomy and is weakly correlated with DCE-MRI kinetic parameters., Level of Evidence: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017;46:1187-1199., (© 2017 International Society for Magnetic Resonance in Medicine.)